scholarly journals Children with atopic dermatitis show increased activity of β‐ glucocerebrosidase and stratum corneum levels of glucosylcholesterol that are strongly related to local cytokine milieu

Author(s):  
Sanja Kezic ◽  
Maeve A. McAleer ◽  
Ivone Jakasa ◽  
Susan M.I. Goorden ◽  
Karen Ghauharali‐van der Vlugt ◽  
...  
2020 ◽  
Vol 21 (6) ◽  
pp. 1958 ◽  
Author(s):  
Ruzica Jurakic Toncic ◽  
Ivone Jakasa ◽  
Suzana Ljubojevic Hadzavdic ◽  
Susan MI Goorden ◽  
Karen JM Ghauharali-van der Vlugt ◽  
...  

Dysfunctional skin barrier plays a key role in the pathophysiology of atopic dermatitis (AD), a common inflammatory skin disease. Altered composition of ceramides is regarded as a major cause of skin barrier dysfunction, however it is not clear whether these changes are intrinsic or initiated by inflammation and aberrant immune response in AD. This study investigated the levels of free sphingoid bases (SBs) sphingosine and sphinganine and their ceramides and glucosylceramide in the stratum corneum (SC) and related them to skin barrier function, disease severity and local cytokine milieu. Ceramides were measured in healthy skin, and lesional and non-lesional skin of AD patients by a novel method based on deacylation of ceramides which were subsequently determined as corresponding sphingoid bases by using liquid chromatography–tandem mass spectrometry (LC–MS/MS). The cytokine levels were determined by multiplex immunoassay. Atopic skin showed increased levels of most investigated markers, predominantly in lesional skin. The largest difference in respect to healthy skin was found for glucosylceramide with respective median values of 0.23 (IQR 0.18–0.61), 0.56 (IQR 0.32–0.76) and 19.32 (IQR 7.86–27.62) pmol/g protein for healthy, non-lesional and lesional skin. The levels of investigated ceramide markers were correlated with disease severity (scoring atopic dermatitis, SCORAD) and skin barrier function (trans-epidermal water loss, TEWL) and furthermore with cytokines involved in innate, Th-1, and Th-2 immune response. Interestingly, the strongest association with SCORAD was found for sphinganine/sphingosine ratio (r = −0.69, p < 0.001; non-lesional skin), emphasizing the importance of SBs in AD. The highest correlation with TEWL was found for glucosylceramide (r2 = 0.60, p < 0.001), which was investigated for the first time in AD. Findings that the changes in SBs and ceramide levels were predominant in lesional skin and their association with disease severity and cytokine levels suggest an immune-system driven effect. a novel analysis method demonstrates a robust and simple approach that might facilitate wider use of lipid biomarkers in the clinics e.g., to monitor (immune) therapy or dissect disease endotypes.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Maja-Lisa Clausen ◽  
S. Kezic ◽  
C. M. Olesen ◽  
T. Agner

AbstractTape stripping is a promising technique for assessment of epidermal biomarkers in inflammatory skin diseases. However, to facilitate its implementation in the clinical practice, a thorough validation regarding sampling strategy is needed. Knowledge of biomarkers variation in concentration across stratum corneum is scarce. Therefore, this study aimed to assess the variability of cytokines across stratum corneum using tape stripping technique by consecutive application of 21 adhesive tapes (D-squame) to lesional and non-lesional skin from 15 patients with atopic dermatitis (AD) and 16 healthy controls. Concentration of cytokines (IL-1α, IL-1b, IL-5, IL-18, IFN-γ, CCL17, CCL22, CCL27, CXCL8, CXCL10, TNF-α, TSLP, VEGFA) was determined in five different depths, using multiplex immunoassay. Comparing tape 4 with tape 21, no cytokine changed significantly in concentration in AD lesional skin. In AD non-lesional skin a small decrease was found for CCL17, CXCL8 and CXCL10. For healthy controls, a decrease was found for IL-1a, IL-1b, VEGFA and an increase for IL-18. Differences were found between AD skin and healthy control skin. Concentration of cytokines was stable across stratum corneum, indicating that sampling of only one tape from the stratum corneum is reliable in reflecting the overall cytokine milieu. Differences between AD and healthy skin confirm robustness of tape stripping for measuring cytokine levels.


2018 ◽  
Vol 180 (3) ◽  
pp. 586-596 ◽  
Author(s):  
M.A. McAleer ◽  
I. Jakasa ◽  
G. Hurault ◽  
P. Sarvari ◽  
W.H.I. McLean ◽  
...  

2016 ◽  
Vol 308 (9) ◽  
pp. 631-642 ◽  
Author(s):  
Nükhet Cavusoglu ◽  
Caroline Delattre ◽  
Mark Donovan ◽  
Sylvie Bourassa ◽  
Arnaud Droit ◽  
...  

1991 ◽  
Vol 283 (4) ◽  
pp. 219-223 ◽  
Author(s):  
A. Yamamoto ◽  
S. Serizawa ◽  
M. Ito ◽  
Y. Sato

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